Although data supporting the use of hyperthermia and radiation for treatment of solid tumors continues to be generated, considerable uncertainty still exists regarding hyperthermia quantification methods and whether there is a relationship between thermal dose and long-term tumor control. In this program, major advances have been made in identification of hyperthermia dosimetry methods which relate to clinical endpoints in retrospective analyses. In order to verify that these methods can be used to prospectively affect treatment outcome it is necessary to conduct trials in which the thermal dose is prospectively controlled. In this project, a quantifiable measure of thermal dose which considers both temperature and treatment time (CEM 43 T90) will be prospectively tested for a relationship with duration of tumor control in dogs with spontaneous soft tissue sarcomas (STS) where delivery of a prescribed thermal dose is possible (heatable tumors). Inclusion of non-heatable tumors in previous studies of hyperthermia has likely diluted the ability to quantify hyperthermia effect. The underlying hypotheses are that: 1) there will be a direct relationship between thermal dose delivered and duration of tumor control in irradiated canine STS, 2) hyperthermia dose escalation can be done safely, and 3) there will be no relationship between thermal dose and metastasis incidence or distribution. At the time of the first hyperthermia treatment, tumors will be defined as heatable or non-heatable based on the ability to deliver at least 2.0 CEM 43 T90 within 2 hrs. Dogs will then be randomized to receive one of two thermal doses; 2-5 CEM 43 T90 or 20-50 CEM 43 T90. Constraints will be placed on HT treatment number and duration. All dogs will also receive 56.25 Gy of fractionated radiotherapy,,with radiation being given before hyperthermia. Dogs will be thoroughly evaluated at regular intervals post- treatment for tumor and normal tissue response and distant disease. Important information generated from this project will allow the relationship between hyperthermia dose and tumor control to be further developed. Such information will be useful for: l) estimation of characteristics of the hyperthermia dose-response curve, 2) determination of the need for development of methods to increase thermal cytotoxicity in tumors, 3) definition of hyperthermia equipment modification criteria to achieve maximum performance, and 4) future clinical trial design criteria.